Inhibitory alpha-adrenergic action of phenylephrine in guinea pig taenia caecum

Abstract

Abstract-Phenylephrine, a selective a-adrenergic stimulant, caused a maximal re laxation of the taenia from guinea pig caecum in the concentration of 10-6 g/ml. Phenylephrine in this concentration did not influence intracellular cyclic AMP and cyclic GMP levels. Although phenylephrine abolished the spontaneous spike discharge, no change was detected in "Ca-uptake and "Ca-efflux on the tissue level after phenyl ephrine. Ca-uptake and Ca-release on the subcellular level were also not influenced by phenylephrine.In Ca free-solution phenylephrine inhibited the response to CaCl2. Phenylephrine increased 42K-efflux in the normally polarized taenia and also in the K-depolarized taenia.Adrenoceptors were classified as a and 3-receptors by Ahlquist (1). As a rule, a receptor is associated with the excitatory functions and 3-receptor with the inhibitory functions. Exceptionally, stimulation of a and (9-receptors in an intestinal smooth muscle causes a relaxation (2). But the inhibitory responses mediated through a and (3-receptors are independent as to mechanical effects and metabolic effects (3).It was reported that stimulation of Q-adrenoceptors elevates the intracellular levels of cyclic AMP and facilitates Ca-accumulation (4). However, little is known of the mechanisms involved in the responses mediated through a-adrenoceptors, except that an a-adrenoceptor stimulant increases K-permeability (5-7). We carried out studies on the effects of an a adrenoceptor stimulant on tissue levels of cyclic nucleotides, Ca-movement and K permeability. MATERIALS AND METHODS Phenylephrinewas used as the a-adrenergic stimulant.Male guinea pigs (300-400 g)were sacrificed by a blow on the neck and two pieces of taenia were removed from one caecum and suspended in two 30 ml organ baths filled with physiological solution kept at 32'C and bubbled with air. One was used for measuring the control levels of cyclic nucleotides and the other for estimating the change in levels of cyclic nucleotides after one min treatment with phenylephrine in the presense of propranolol. They were frozen in liquid nitrogen.Cyclic AMP was assayed with the method of Gilman (8)

Accumulation of Potassium and Calcium in Rat Myocardium Exposed to α‐1‐Adrenoceptor Stimulation

“…a-I-Adrenoceptor stimulation caused a net loss of potassium from isolated guinea-pig hepatocytes, and a net uptake of potassium into rat hepatocytes (Burgess et al 1981), and a transient net calcium efflux from perfused rat liver (Reinhart et al 1982). Iwayama et al (1979) found no detectable change in 45Ca-uptake or efflux in guinea pig taenia caecum after a-adrenergic stimulation. In contrast, they found that phenylephrine increased 42Kefflux.…”

Increased Intracellular Potassium and Water Contents in Rat Heart after α‐1‐Adrenoceptor Stimulation

“…In one study rat hepatocytes had a net uptake of potassium in contrast to isolated guinea-pig hepatocytes which had a net potassium loss (Burgess et al 1981). In guinea pig teania caecum (Iwayama et al 1979) and in rat parotid gland tissue (It0 et al 1982), increased potassium efflux was found to be an a-adrenoceptor mediated effect.…”

Mechanisms of Inhibitory Action of Phenylephrine in Guinea-Pig Taenia Coli

“…On the other hand, phenyle phrine exerted no effect on the 45Ca-efflux from the partly depolarized taenia coli of guinea pigs, indicating that the a-agonist induced relaxation of the smooth muscle is not related to the acceleration of Ca-efflux. Iwayama et al (9) have studied the effect of phenylephrine on the cellular calcium movements in the polarized taenia coli, demonstrating that phenylephrine does not inhibit the cellular 45Ca-uptake. In addition, they observed that phenylephrine caused the hyperpolarization in the polarized taenia coli smooth muscle.…”

“…It is well documented that the relaxation of the taenia coli of guinea pigs in response to a-agonists is related to the acceleration of K+ flux (8,9,22), while the role of Na+ on the a-adrenergic action remains nuclear. The present results demonstrated that the relaxant action of phenylephrine was completely lost in the Na-free solution in which Na+ was replaced by substitutes such as sucrose, choline and Tris, but restored in proportion to the amount of Na+ readded to the Na-free solution.…”